Version July 2025
Severe and life-threatening neutropenia, including fatal neutropenic sepsis and fatal neutropenic fever, has occurred in patients receiving irinotecan (liposomal) in combination with oxaliplatin, fluorouracil, and leucovorin, and in combination with fluorouracil and leucovorin. Withhold irinotecan (liposomal) for absolute neutrophil count below 1,500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.
Severe and life-threatening diarrhea has occurred in patients receiving irinotecan (liposomal) in combination with oxaliplatin, fluorouracil, and leucovorin, and in combination with fluorouracil and leucovorin. Do not administer irinotecan (liposomal) to patients with bowel obstruction. Withhold irinotecan (liposomal) for diarrhea of grade 2 to 4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity.
Dosage guidance:
Safety: Irinotecan (liposomal) and irinotecan (conventional) are NOT interchangeable; dosing differs between formulations; verify intended product and dose prior to preparation and administration.
Clinical considerations: Irinotecan (liposomal) is associated with a moderate emetic potential (Ref). Premedicate with a corticosteroid and an antiemetic 30 minutes prior to infusion.
Biliary tract cancer, metastatic, progressive (off-label use): IV: 70 mg/m2 once every 2 weeks (in combination with fluorouracil and leucovorin); continue until disease progression or unacceptable toxicity (Ref). Refer to the protocol or institutional guidance for additional details of off-label dosing.
Pancreatic adenocarcinoma, metastatic:
In combination with oxaliplatin, fluorouracil, and leucovorin (first-line treatment; NALIRIFOX regimen): IV: 50 mg/m2 once every 2 weeks; continue until disease progression or unacceptable toxicity (Ref). Note: For the first-line treatment of metastatic pancreatic adenocarcinoma, irinotecan (liposomal) dose is not impacted by UGT1A1*28 allele genotype.
In combination with fluorouracil and leucovorin (progressive disease): IV: 70 mg/m2 once every 2 weeks; continue until disease progression or unacceptable toxicity (Ref). Note: Reduce initial starting dose to 50 mg/m2 in patients known to be homozygous for the UGT1A1*28 allele; the dose may be increased to 70 mg/m2 as tolerated in subsequent cycles.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, a population pharmacokinetic analysis showed no effect on total irinotecan and SN-38 exposure in patients with mild to moderate renal impairment.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (insufficient data).
Bilirubin > ULN: There are no dosage adjustments provided in the manufacturer's labeling (there is no recommended dose). No data are available regarding use in patients with bilirubin >2.8 mg/dL.
American Society of Clinical Oncology guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
In combination with oxaliplatin, fluorouracil, and leucovorin (first-line treatment; NALIRIFOX regimen):
|
a Discontinue irinotecan (liposomal) if unable to tolerate after third dose reduction. | |
|
Usual (initial dose) |
50 mg/m2 IV every 2 weeks |
|
First dose reduction level |
40 mg/m2 IV every 2 weeks |
|
Second dose reduction level |
32.5 mg/m2 IV every 2 weeks |
|
Third dose reduction levela |
25 mg/m2 IV every 2 weeks |
|
Adverse reaction |
Severity |
Irinotecan (liposomal) dosage modification |
|---|---|---|
|
a According to the manufacturer, irinotecan (liposomal) should not be resumed until ANC is ≥2,000/mm3 and platelets are ≥100,000/mm3. | ||
|
b No dosage modification is necessary for asthenia, alopecia, and grade 3 anorexia. | ||
|
Hematologic toxicity a | ||
|
Neutropenia |
ANC <1,500/mm3 or neutropenic fever |
Withhold irinotecan (liposomal) until ANC ≥1,500/mm3. Resume irinotecan (liposomal) at a reduced dose for grade 3 or 4 neutropenia or neutropenic fever in subsequent cycles following recovery. |
|
Nonhematologic toxicity | ||
|
Anaphylactic reaction or other severe hypersensitivity reaction |
Any (first occurrence) |
Permanently discontinue irinotecan (liposomal). |
|
Cardiovascular toxicity |
Grade ≥2 (first occurrence) |
Discontinue irinotecan (liposomal). |
|
CNS toxicity (neurocerebellar toxicity) |
Any (first occurrence) |
Discontinue irinotecan (liposomal). |
|
Dermatologic toxicity (hand-foot syndrome) |
Grade 3 or 4 (first occurrence) |
Discontinue irinotecan (liposomal). |
|
Diarrhea |
Any |
Administer IV or SUBQ atropine 0.25 to 1 mg (unless clinically contraindicated) for early-onset diarrhea of any severity. Administer loperamide for late-onset diarrhea of any severity. Follow local institutional guidelines for treatment of diarrhea that does not improve within 48 hours (eg, diphenoxylate hydrochloride plus atropine or octreotide). |
|
Grade 2 to 4 |
Withhold irinotecan (liposomal) until recovery to grade 1; resume irinotecan (liposomal) at a reduced dose. | |
|
Interstitial lung disease |
Suspected (eg, new or progressive dyspnea, cough, and fever) |
Withhold irinotecan (liposomal) pending diagnostic evaluation. |
|
Confirmed (first occurrence) |
Discontinue irinotecan (liposomal). | |
|
Nausea and vomiting |
Grade ≥3 |
Withhold irinotecan (liposomal) until recovery to ≤ grade 1. Upon recovery, reduce dose only if ≥ grade 3 nausea and vomiting occur despite optimal antiemetic therapy. |
|
Other adverse reactionsb |
Grade 3 or 4 |
Withhold irinotecan (liposomal) until recovery to ≤ grade 1; resume irinotecan (liposomal) at a reduced dose. |
In combination with fluorouracil and leucovorin (progressive disease):
|
Patients receiving full dose irinotecan (liposomal) |
Patients homozygous for UGT1A1*28 without previous increase to 70 mg/m2 | |
|---|---|---|
|
a Discontinue irinotecan (liposomal) if unable to tolerate after second dose reduction. | ||
|
Usual (initial dose) |
70 mg/m2 IV every 2 weeks |
50 mg/m2 IV every 2 weeks |
|
First dose reduction level |
50 mg/m2 IV every 2 weeks |
43 mg/m2 IV every 2 weeks |
|
Second dose reduction levela |
43 mg/m2 IV every 2 weeks |
35 mg/m2 IV every 2 weeks |
|
Adverse reaction |
Severity |
Irinotecan (liposomal) dosage modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Neutropenia |
ANC <1,500/mm3 or neutropenic fever |
Withhold irinotecan (liposomal) until ANC ≥1,500/mm3. Resume irinotecan (liposomal) at a reduced dose for grade 3 or 4 neutropenia or neutropenic fever in subsequent cycles following recovery. |
|
Nonhematologic toxicity | ||
|
Anaphylactic reaction or other severe hypersensitivity reaction |
Any (first occurrence) |
Permanently discontinue irinotecan (liposomal). |
|
Diarrhea |
Any |
Administer IV or SUBQ atropine 0.25 to 1 mg (unless clinically contraindicated) for early-onset diarrhea of any severity. Administer loperamide for late-onset diarrhea of any severity. Follow local institutional guidelines for treatment of diarrhea that does not improve within 48 hours (eg, diphenoxylate hydrochloride plus atropine or octreotide). |
|
Grade 2 to 4 |
Withhold irinotecan (liposomal) until recovery to grade 1; resume irinotecan (liposomal) at a reduced dose. | |
|
Interstitial lung disease |
Suspected (eg, new or progressive dyspnea, cough, and fever) |
Withhold irinotecan (liposomal) pending diagnostic evaluation. |
|
Confirmed (first occurrence) |
Discontinue irinotecan (liposomal). | |
|
Other adverse reactions |
Grade 3 or 4 |
Withhold irinotecan (liposomal) until recovery to ≤ grade 1; resume irinotecan (liposomal) at a reduced dose. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages reported as part of combination chemotherapy regimens.
>10%:
Cardiovascular: Embolism (11%; serious: 4%), peripheral edema (16%)
Dermatologic: Alopecia (14%), skin rash (11%)
Endocrine & metabolic: Dehydration (8% to 11%; serious: 3%), hypoalbuminemia (43%), hypocalcemia (32%), hypokalemia (32% to 62%), hypomagnesemia (35%), hyponatremia (27%), hypophosphatemia (29%), increased serum sodium (11%), weight loss (17% to 22%)
Gastrointestinal: Abdominal pain (35%; serious: 3%), constipation (25%), decreased appetite (37% to 44%), diarrhea (59% to 72%, grades 3/4: 13% to 22%; early onset: 30%, grades 3/4: 3%; late onset: 43%, grades 3/4: 9%), nausea (51% to 59%; grades 3/4: 8% to 12%), stomatitis (28% to 32%; grades 3/4: 4%), vomiting (40% to 52%; grades 3/4: 7% to 11%)
Hematologic & oncologic: Anemia (91% to 97%; grades 3/4: 6% to 10%), hemorrhage (11%; grades 3/4: 2%), leukopenia (62%; grades 3/4: 8%), lymphocytopenia (64% to 81%; grades 3/4: 11% to 27%), neutropenia (52% to 56%; grades 3/4: 20% to 26%), thrombocytopenia (41% to 55%; grades 3/4: 2%)
Hepatic: Increased serum alanine aminotransferase (40% to 51%), increased serum alkaline phosphatase (45%), increased serum aspartate aminotransferase (38%)
Nervous system: Asthenia (≤56%), fatigue (≤62%)
Neuromuscular & skeletal: Musculoskeletal pain (18%)
Renal: Increased creatinine clearance (18%)
Miscellaneous: Fever (11% to 23%)
1% to 10%:
Endocrine & metabolic: Increased serum potassium (8%)
Gastrointestinal: Gastroenteritis (3%), gastrointestinal obstruction (≤4%), gastrointestinal stenosis (≤4%)
Hematologic & oncologic: Febrile neutropenia (≤3%; grades 3/4: ≤3%)
Hypersensitivity: Infusion-related reaction (3%)
Infection: Neutropenic sepsis (≤3%), sepsis (2% to 4%), septic shock (≥2%)
Nervous system: Cerebrovascular accident (3%)
Renal: Acute kidney injury (≥2%)
Respiratory: Dyspnea (8%), pneumonia (2%)
<1%: Dermatologic: Nail disease
Frequency not defined:
Infection: Infection
Nervous system: Peripheral neuropathy
Postmarketing:
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema)
Respiratory: Interstitial lung disease
Severe hypersensitivity or anaphylaxis to irinotecan (liposomal), irinotecan hydrochloride, or any component of the formulation.
Canadian labeling (additional contraindications not in the US labeling): Breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Irinotecan (liposomal) may cause severe or life-threatening neutropenia, including severe or life-threatening neutropenic fever and fatal neutropenic sepsis. In the NAPOLI-1 trial, the incidence of grade 3 or 4 neutropenia was higher in patients of Asian descent (compared to White patients); however, rates of grade 3 or 4 neutropenia were similar between groups in the NAPOLI-3 trial.
• GI toxicity: Irinotecan (liposomal) may cause severe and life-threatening diarrhea. Early-onset diarrhea occurs within 24 hours of chemotherapy and may be associated with other symptoms of cholinergic reaction. Late-onset diarrhea occurs more than 24 hours following chemotherapy. A patient may experience both early- and late-onset diarrhea. Do not administer irinotecan (liposomal) to patients with bowel obstruction.
• Hypersensitivity reactions: Irinotecan (including irinotecan liposomal) may cause severe hypersensitivity reactions (including anaphylaxis).
• Pulmonary toxicity: Irinotecan (including irinotecan liposomal) may cause severe and fatal interstitial lung disease, including pneumonitis. Risk factors include preexisting lung disease, use of pneumotoxic medications, colony-stimulating factors, or previous radiation therapy.
Special populations:
• Reduced UGT1A1 activity: Patients homozygous for the UGT1A1*28 allele (*28/*28) are at increased risk of severe or life-threatening neutropenia with irinotecan due to poor metabolism of UGT1A1; UGT1A1-poor metabolizers have increased systemic exposure to SN-38 (active metabolite). In clinical studies (NAPOLI-3), the frequency of grade 3 or 4 neutropenia and dose reductions secondary to treatment-related adverse effects were higher in patients homozygous for the UGT1A1*28 allele when compared to those that were nonhomozygous for the UGT1A1*28 allele (rates of grade 3 or 4 neutropenia were similar when dose reduction from 70 mg/m2 to 50 mg/m2 in patients homozygous for UGT1A1*28 was implemented in NAPOLI-1).
Dosage form specific issues:
• Liposomal vs conventional formulation dosing: Irinotecan (liposomal) and irinotecan (conventional) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injectable, Intravenous:
Onivyde: 43 mg/10 mL (10 mL) [contains mpeg-2000-dspe (methoxy-terminated peg)]
No
Injection (Onivyde Intravenous)
43 mg/10 mL (per mL): $357.48
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injectable, Intravenous:
Onivyde: 43 mg/10 mL (10 mL) [contains mpeg-2000-dspe (methoxy-terminated peg)]
Irinotecan (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: Administer by IV infusion over 90 minutes. Premedicate with a corticosteroid and an antiemetic 30 minutes prior to infusion.
Administration sequence :
In combination with oxaliplatin, leucovorin, and fluorouracil (first-line treatment; NALIRIFOX regimen): Administer irinotecan (liposomal) first, followed by oxaliplatin, then followed by leucovorin, then followed by fluorouracil.
In combination with fluorouracil and leucovorin (progressive disease): Administer irinotecan (liposomal) first, followed by leucovorin, then followed by fluorouracil.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Pancreatic adenocarcinoma, metastatic:
First-line treatment (in combination with oxaliplatin, fluorouracil, and leucovorin) of metastatic pancreatic adenocarcinoma in adults.
Treatment (in combination with fluorouracil and leucovorin) of metastatic pancreatic adenocarcinoma in adults with disease progression following gemcitabine-based therapy.
Limitations of use: Irinotecan (liposomal) is not indicated as a single agent for the treatment of metastatic pancreatic adenocarcinoma.
Guideline recommendations:
The American Society of Clinical Oncology (ASCO) guidelines for metastatic pancreatic cancer recommend fluorouracil in combination with irinotecan (liposomal) as preferred second-line therapy in patients with Eastern Cancer Cooperative Group (ECOG) performance status (PS) of 0 or 1, a relatively favorable comorbidity profile, preference for aggressive therapy, a suitable support system, and access to a chemotherapy port/infusion pump management service who received an alternative (gemcitabine-based) first-line therapy. Irinotecan (liposomal) may be added to fluorouracil (with proactive dose/schedule adjustments to minimize toxicities) as second-line therapy for patients with a PS of 2 or a comorbidity profile prohibiting more aggressive therapy (ASCO [Sohal 2020]).
According to ASCO guidelines for locally advanced, unresectable pancreatic cancer, if disease progression occurs following induction with an initial systemic combination therapy regimen, treatment according to guidelines for metastatic pancreatic cancer should be offered (in appropriate patients) (ASCO [Balaban 2016]).
Biliary tract cancer, metastatic, progressive
Liposomal formulation (Onivyde) may be confused with the conventional formulation (Camptosar)
Irinotecan (liposomal) may be confused with irinotecan (conventional), topotecan
Onivyde may be confused with Oncaspar, Opdivo
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; liposomal forms with conventional counterparts) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Irinotecan (liposomal) and irinotecan (conventional) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
Substrate of BCRP, CYP3A4 (Major), OATP1B1/1B3, P-glycoprotein (Minor), UGT1A1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Atazanavir: May increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Capecitabine: Irinotecan Products may increase nephrotoxic effects of Capecitabine. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Irinotecan Products. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Itraconazole: May increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid
Ketoconazole (Systemic): May increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Phenobarbital-Primidone: May decrease serum concentration of Irinotecan Products. Management: Avoid administration of phenobarbital or primidone during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor closely for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sacituzumab Govitecan: Irinotecan Products may increase adverse/toxic effects of Sacituzumab Govitecan. Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
St John's Wort: May decrease serum concentration of Irinotecan Products. St John's Wort may decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Management: Avoid administration of St John's wort during irinotecan treatment, and consider substituting non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Telotristat Ethyl: May decrease active metabolite exposure of Irinotecan Products. Risk C: Monitor
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tobacco (Smoked): May decrease active metabolite exposure of Irinotecan Products. Risk C: Monitor
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
UGT1A1 Inhibitors: May increase active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase serum concentration of Irinotecan Products. Risk X: Avoid
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Patients who could become pregnant should use effective contraception while receiving treatment and for 7 months following the last irinotecan (liposomal) dose. Patients with partners who could become pregnant should use condoms during therapy and for 4 months following the last irinotecan (liposomal) dose.
Based on the mechanism of action as well as animal data using irinotecan (conventional), in utero exposure to irinotecan (liposomal) may cause fetal harm.
It is not known if irinotecan (liposomal) is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for 1 month following the last irinotecan (liposomal) dose.
Patients should maintain adequate hydration, avoid lactose-containing products, and eat frequent small meals with a low-fat diet to minimize the risk of severe diarrhea with irinotecan (liposomal).
CBCs on days 1 and 8 of each cycle and more frequently if clinically indicated; bilirubin, electrolytes (with severe diarrhea). Monitor bowel movements (diarrhea episodes) and hydration status; monitor for respiratory signs/symptoms of pulmonary toxicity (eg, new or progressive dyspnea, cough, and fever) in patients with risk factors before and during therapy and/or hypersensitivity reactions.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Irinotecan (liposomal) is a topoisomerase 1 inhibitor encapsulated in a lipid bilayer (liposome). Irinotecan and its active metabolite (SN-38) bind reversibly to topoisomerase I-DNA complex preventing re-ligation of the cleaved DNA strand. This results in the accumulation of cleavable complexes and double-strand DNA breaks. As mammalian cells cannot efficiently repair these breaks, cell death consistent with S-phase cell cycle specificity occurs, leading to termination of cellular replication.
Distribution: Vd (total irinotecan): 3.63 L (50 mg/m2) to 4.23 L (70 mg/m2); Vd (total SN-38): 3.46 L (50 mg/m2) to 4.06 L (70 mg/m2); 95% of irinotecan remains liposome-encapsulated.
Protein binding: <1%
Metabolism: Irinotecan hydrochloride: Primarily hepatic to SN-38 (active metabolite) by carboxylesterase enzymes; may also undergo CYP3A4-mediated metabolism to inactive metabolites (one of which may be hydrolyzed to release SN-38). SN-38 undergoes conjugation by UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite. SN-38 is increased by UGT1A1*28 polymorphism (10% of North Americans are homozygous for UGT1A1*28 allele).
Half-life elimination: Total irinotecan: 1.87 days (70 mg/m2) to 1.93 days (50 mg/m2).
Excretion: Urine: Irinotecan hydrochloride (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%)
Hepatic function impairment: AUC of total SN-38 was increased by 32% in patients with bilirubin concentrations of 1.14 mg/dL versus patients with bilirubin levels of 0.44 mg/dL.
Race/Ethnicity: Irinotecan AUC was 32% lower in patients of Asian descent when compared to other patients.
Sex: Irinotecan and SN-38 AUC were 28% and 32% higher, respectively, in female patients than in male patients.
